In this study, the efficiency of a suspect screening strategy using liquid chromatography-high resolution mass spectrometry (LC-HRMS) without the prior purchase of reference standards was systematically optimized and evaluated for assessing the exposure of rarely investigated pesticides and their transformation products (TPs) in 76 surface water samples. Water-soluble and readily ionizable (electrospray ionization) substances, 185 in total, were selected from a list of all insecticides and fungicides registered in Switzerland and their major TPs. Initially, a solid phase extraction-LC-HRMS method was established using 45 known, persistent, and high sales volume pesticides. Seventy percent of these target substances had limit of quantitation (LOQ) < 5 ng L(-1). This compound set was then used to develop and optimize a HRMS suspect screening method using only the exact mass as a priori information. Thresholds for blank subtraction, peak area, peak shape, signal-to-noise, and isotopic pattern were applied to automatically filter the initially picked peaks. The success rate was 70%; false negatives mainly resulted from low intense peaks. The optimized approach was applied to the remaining 140 substances. Nineteen additional substances were detected in environmental samples, two TPs for the first time in the environment. Sixteen substances were confirmed with reference standards purchased subsequently, while three TP standards could be obtained from industry or other laboratories. Overall, this screening approach was fast and very successful and can easily be expanded to other micropollutant classes for which reference standards are not readily accessible such as TPs of household chemicals.